Secretory functions of the uterine, cervical and vaginal mucous cells have a profound impact on the function and health of the reproductive tract. For example, the quality and quantity of cervical mucus changes throughout the menstrual cycle and such changes dramatically influence fertility. Under the influence of rising estrogen levels, cervical mucus becomes thin, allowing the passage of spermatozoa. Later in the menstrual cycle, as progesterone levels increase, mucus becomes thick and hostile to sperm penetration, thereby closing the window of fertility. Such thickening of cervical mucus is thought to be one of the primary modes of contraceptive action for progestin-only contraceptives.
Estrogen stimulates the production of thin, isotonic mucus, with increased amounts of high molecular weight glycoproteins. Cervical mucus contains 98% water at mid cycle and 90% water at other times. Cervical mucus is also rich in metallic ions, enzymes (such as alkaline phosphatase, etc.), soluble proteins and salts. The gel phase of cervical mucus contains a high molecular weight glycoprotein called mucin. Mucin forms micelles that cross-link by disulfide bridges. Estrogen and progestogens control the arrangement of these micelles. These micellar arrangements influence the rheological properties of mucus. See Kopito et al. Water and electrolytes in human cervical mucus. Fertil. Steril. 1973; 24:499–506; Fordney-Settlage, D. A review of cervical mucus and sperm interactions in humans. Int. J. Fertil. 1981; 26:161–169.
As estrogen levels fall in the menopause, estrogen dependent tissue will start to involute and take on the characteristic appearance of estrogen deprivation. Cervical mucus levels diminish and vaginal mucosa regresses during menopause. With aging, the vagina becomes shortened, ruggae disappear, and elasticity is lost. Vaginal secretion becomes scanty. When estrogen is provided, some of these effects are reversed: the cervix may secrete more mucus and the vaginal mucosa may regain lost layers. However, the symptoms often do not disappear completely, in part because the amount of estrogen provided for hormone replacement is lower than circulating estrogen levels during a normal menstrual cycle.
Approximately 40% of postmenopausal women experience atrophic vaginitis or vaginal dryness. During vaginal atrophy, the vaginal epithelium decreases in thickness, hydration, rugae (folds), and blood flow. Causes of atrophic vaginitis include a decrease in the amount of estrogen present both locally and systemically as well as environmental factors such as chemotherapy, antihistamines, smoking cigarettes, excessive exercise, and perineal products (i.e. douches, deodorants, and perfumes). Estrogens or hormone replacement therapies (HRTs) are effective in reducing vaginal dryness. However, possible dangerous side effects include a higher incidence of breast cancer, endometrial cancer, blood clots, nausea, breast tenderness, and headache. Products that are available over-the-counter include lubricants such as Astroglide and KY Lubricating Jelly as well as moisturizers such as Replens and KY Long Lasting Moisturizer. These products, which are mostly water in composition, provide only temporary relief (1–2 days) for symptoms and provide virtually no long-term benefits to the vaginal tissue.
Therefore, vaginal dryness and lack of lubrication is a problem, particularly after menopause. Stimulation of cervical mucus production can help alleviate vaginal dryness, and can also augment the action of exogenously administered estrogen to alleviate vaginal dryness. Accordingly, compositions and methods for modulating mucus levels in the human vagina are needed.